title: Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  The identification of new biomarkers to predict the aggressiveness of hepatocellular carcinoma (HCC) and supplement the current set of prognosis and treatment algorithms is an important clinical need. Extracellular microRNAs (miRNAs) circulating in the blood are a new class of highly promising disease markers.
  
  
  OBJECTIVE
  Here we investigated the prognostic potential of miR-1 and miR-122 in sera from patients with HCC.
  
  
  METHODS
  RNA was extracted from 195 sera of HCC patients and 54 patients with liver cirrhosis, obtained at the time of study enrolment. miR-1 and miR-122 levels were correlated with overall survival (OS), Cancer of the Liver Italian Program (CLIP) score, Barcelona Clinic Liver Cancer stage, clinical chemistry parameters and tumor specific treatment.
  
  
  RESULTS
  Patients with higher miR-1 and miR-122 serum levels showed longer OS than individuals with lower miR-1 and miR-122 serum concentrations (hazard ratio [HR] 0.440, 95% confidence interval [CI] 0.233-0.831, P=0.011 for miR-1 and HR 0.493, 95% CI 0.254-0.956, P=0.036 for miR-122, respectively). Serum miR-1 and miR-122 concentrations did not differ significantly between patients with HCC and liver cirrhosis. An age-, sex-, tumor stage and treatment-adjusted multivariate Cox regression analysis revealed that miR-1 serum levels (HR 0.451, 95% CI 0.228-0.856, P=0.015) were independently associated with OS, whereas serum miR-122 was not. miR-1 serum levels showed no relevant correlation with clinical chemistry liver parameters, whereas serum miR-122 correlated with clinical chemistry parameters of hepatic necroinflammation, liver function and synthetic capacity.
  
  
  CONCLUSIONS
  Our data indicate that serum miR-1 is a new independent parameter of OS in HCC patients and may therefore improve the predictive value of classical HCC staging scores.
authors.affiliation: Department of Medicine I, Division of Gastroenterology and Hepatology, Johann Wolfgang Goethe University Hospital Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Köberle
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Pleli
authors.forename: Jörg
authors.initials: J
authors.lastname: Trojan
authors.forename: Esther
authors.initials: E
authors.lastname: Imelmann
authors.forename: Jan
authors.initials: J
authors.lastname: Peveling-Oberhag
authors.forename: Martin-Walter
authors.initials: MW
authors.lastname: Welker
authors.forename: Mohammed
authors.initials: M
authors.lastname: Elhendawy
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Albrecht
authors.initials: A
authors.lastname: Piiper
authors.forename: Oliver
authors.initials: O
authors.lastname: Waidmann
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C544547:MIRN1 microRNA, human; C531907:MIRN122 microRNA, human; D035683:MicroRNAs
keywords: HCC; Prognostic marker; miR-1; miR-122; microRNA